Abstract
Fibroblast growth factor 23 (FGF23) has recently been identified as a critical regulatory factor in phosphate (P) metabolism. Although the exact molecular mechanism of FGF23 synthesis through sensing the concentration of P is yet to be determined, experimental and clinical data indicate the influential role of FGF23 in P and calcium (Ca) homeostasis. Here, we extended our previous mathematical model in calcium regulation and examined the conceivable roles of FGF23 in mineral metabolism. We assumed that the level of FGF23 was controlled through the concentrations of P and calcitriol in serum, and its actions such as lowering of the renal threshold for P, inhibition of the production of calcitriol in the kidney tubule, and inhibition of the production of parathyroid hormone (PTH) were included. Comparisons between the models with and without FGF23 demonstrate a complex interplay of FGF23 with calcitriol and PTH. In consistent with the model, our in vitro experimentation indicates that expression of FGF23 is activated in the presence of P though a G-protein linked receptor. We expect that further efforts on modeling and experimental evaluation would contribute to diagnosing patients with metabolic diseases such as osteoporosis and chronic kidney diseases, and developing FGF23-linked treatment strategies.
Highlights
The FGF family consists of 22 members for various functions in embryonic development, cellular proliferation and differentiation, tissue repair, and tumor growth and invasion
Based on the above mentioned formulation of the expression and actions of Fibroblast growth factor 23 (FGF23), we first evaluated the effects of the stepwise increase in the secretion of FGF23 on the regulatory and homeostatic variables such as the concentrations of parathyroid hormone (PTH), calcitriol, Ca, and P in serum as well as the absorption and excretion amounts of Ca and P
In order to characterize the chronic effects of the increase in FGF23, we evaluated the pseudo steady-state values (2000 h) (Fig. 3)
Summary
The FGF family consists of 22 members for various functions in embryonic development, cellular proliferation and differentiation, tissue repair, and tumor growth and invasion. We included the actions of FGF23 to a previously published mathematical model of calcium and phosphate metabolism[8] and investigated the potential influence of FGF23 on the observable state variables such as the serum concentrations of PTH, calcitriol, Ca, P, and the urinary excretion of Ca and P.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
